BIOLOGISTS HAVE ACHIEVED so MUCH IN THE LAST CENTURY,

AND PARTICULARLY IN THE LAST TWENTY-FIVE YEARS, THAT YOU

MAY WONDER WHY I CHOSE TO TALK *ABOUT THE FUTURE

RATHER THAN

AGE, AT THE

APPROPRIATE

LUCKY ENOUG

WHAT OTHERS

CONCENTRATE ON THE PRESENT,  ESPECIALLY AT MY

THRESHOLD OF RETIREMENT, IT WOULD SEEM MORE
TO SUM UP THE ACHIEVEMENTS THAT 1 HAVE BEEN

H TO WITNESS RATHER THAN TRYING TO FORECAST

WILL BE DOING AFTER MY TIME,

MY REASONS FOR CONCENTRATf $G ;N THE FUTUJ~~~~~ER THAN
THE PAST ARE TWO, THE FIRST T GENERAL 0;~~: CAN BEST
EXPRESS IN THE WORDS OF BERTRAND RUSSELL: Gi T IS IMPORTANT

TO CARE IMMENSELY ABOUT THINGS THAT ARE GOING TO HAPPEN
            J
      L WHAT RUSSELL MEANT, OF COURSE, IS THAT
AFTER ONE IS DEAD,

THE TEST OF ONE'S HUMANITY IS TO IDENTIFY, NOT WITH ONE TIME
       R ONE JOB/BUT WITH THE CONTINUITY OF THE

           ENTERPRISE OF MANKIND,  SUCH BELIEF WAS SURELY
               /
YPART OF THE SEC%-OFOFE THAT MADE RUSSELL LIVE

TO BE A STURDY 98!

MY SECOND REASON FOR LOOKING AT THE FUTURE IS THAT THERE

HAS RECENTLY BEEN A CERTAIN GLOOM IN THE WORLD OF BIOLOGY,
IT MAY JUST BE THE GLOOM THAT FOLLOWS EV/ER&Su~F~IT OF SUCCESS,
BUT IT MUST BE TAKEN SERIOUSLY BECAUSE IT<NDICA+/We
UNHEALTHY SITUATION,            ET qc Ah'


2

  ON THE ONE HAND, THERE ARE THE PROPHETS OF DOOM, WHO

TELL US THAT ALL THAT WAS EXCITING TO SOLVE IN BIOLOGY HAS

BEEN SOLVED: THAT, ALAS, NO NEW COSMIC LAWS HAVE BEEN

DISCOVERED; AND THAT ALL THAT REMAINS TO BE DONE IS TO MOP

UP -- EXCEPT PERHAPS FOR EXPLAINING THE HUMAN BRAIN, A

SMALL ORDER INDEED; LIKE SAYING THAT, HAVING LEARNED TO
CLIMB BEACON HILL, ALL THAT REMAINS IS TO CLIMB ANNAPURNA!
THIS TREND IS, OF COURSE, PURE WELTSCHMERZ OR SNOBBERY, AND

1 SEE LITTLE DANGER OF ITS SPREADING FAR/AMONG THE NEW

GENERATION OF BIOLOGISTS,              /

THE SECOND SOURCE OF QUESTIONING, ON THE OTHER HAND, IS

MORE SERIOUS AND MORE DANGEROUS,  IT IS THE %O-WHATN TYPE

OF QUESTIONING,  IT IS THE SOURCE OF A REAL CRISIS, OR

RATHER PSEUDO-CRISIS, WHICH TAKES THE FORM OF ANTI-REDUCTIONISM

OF AN ATTACK ON SCIENTIFIC REDUCTIONISM, AN ATTACK CARRIED

OUT IN THE NAME OF WHAT IS VARIOUS  Y
        @vh  CALLED WHOLISM OR

INTEGRATIONISM, THE ARGUMENTFHE ANTI-R~~IJJ;IONISTS IS
SIMPLE: THE MORE 2#4! MOLECULAR BIOLOGISTS F#$+OUT ABOUT THE
MOLECULAR STRUCTURE OF ORGANISMS, AND THE RELATION OF THAT

STRUCTURE TO ORGANIC FUNCTIONS, THE MORE THE INTEGRATIONISTS
COMPLAIN THAT WHATFVER THE REDUCTIONISTS FIND @I$@ ISXTHE

IMPORTANT PART OF BIOLOGY,  WE ARE TOLD THAT THE ORGANISM,

AND THE HERD, AND THE SPECIES, AND THE ECOLOGICAL NICHE ARE

WHAT MATTERS,  IT ALL SOUNDS AS IF THESE MOST COMPLEX LEVELS

OF ORGANIZATION DERIVED THEIR REALITY, NOT FROM THEIR


3

COMPONENT ELEMENTS, WITH THEIR SPECIFIC MOLECULAR STRUCTURES

AND FUNCTIONS, BUT FROM SOME ALMOST MYSTICAL ELEMENT OF
NWHOLENESS" COMING SOMEHOW FROM SOMEWHERE ELSE -- IN OTHER

WORDS,  THE MYTH OF NEMERGENCE,N To CITE ONE EXAMPLE, AN

EMINENT WHOLISTIC BIOLOGIST WHO READ THE MANUSCRIPT OF A

BOOK OF MINE, WROTE ME A SERIOUS AND URGENT PLEA TO INTRODUCE
-AT LEAST THE IDEA THAT "SOMETHING SPECIAL,"

SOMETHING OUTSIDE CURRENT EVOLUTIONARY THEORY, MAY HAVE ENTERED

THE PICTURE TO MAKE POSSIBLE THE EMERGENCE OF MAN,  SINCE I AM

AGAINST DISCRIMINATION OF ANY SORJ,I WONDERED% WHY SHOULDN'T
THE HONEY BEES, OR THE BIRDS OF PARADISE, OR THE WHALES / FEEL
ENTITLED TO THE SAME EXCEPTIONALITY WITHIN EVOLUTION, JUST
BECAUSE THEY DON'T HAVE A CHANCE TO REVIEW MANUSCRIPTS PRIOR
TO PUBLICATION?

THE EMPHASIS ON THE COMPLEX AND THE HARD-TO-EXPLAIN AS

BEING THE ONLY VALID CENTERS OF INTEREST
                         ,- ___- _ .--- -...  ~~~-- / IMPLIES A MYSTIC//-
ATTITUDE, ALMOST A HOPE THAT BRIDGES WILL &&BE FOUND BETWEEN'
THE COMPLEX, INTEGRATIVE LEVELS AND THE SIMPLER LEVELS OF

INTERPRETATION,  1 USED TO ATTRIBUTE, CYNICALLY, THE ANTI-

REDUCTIONIST ATTITUDE OF ORGANISMIC BIOLOGISTS TO AN
           /'
UNWILLINGNESS TO LEARN BIOCHEMISTRY,  BUT ANTI-REDUCTIONISM

IS NOT JUST AN ODDITY AMONG BIOLOGISTSfi  IT IS AN ATTITUDE

THAT BIOLOGISTS BORROW, UNCONSCIOUSLY, FROM THE SOCIAL

SCIENCES, WHERE A NONREDUCTIONIST, PHENOMENOLOGICAL APPROACH

IS NECESSARY AND JUSTIFIED,  LET ME ILLUSTRATE WHAT I MEAN

WITH AN EXAMPLE,


4

I RECENTLY HAD THE EXPERIENCE OF DINING WITH A GROUP OF

DISTINGUISHED SOCIAL PSYCHOLOGISTS,  DURING DINNER, I BROUGHT

UP CONVERSATIONALLY SOME FACTS OF NEUROPHYSIOLOGY THAT 1 HAD

LEARNED A FEW DAYS EARLIER AND 1 HAD FO ND  XCITING, ANDF
                    SW!2 YF
                                    t-h. ,w
THOUGHT WOULD INTEREST MY COMPANIONS,  "y HERE WAS AN
                               A

EMBARRASSED               HAD MENTIONED DEATH AT A WAKE;
OR AS IF 1 HAD             DEVIL IN THE HOME OF A METHODIST

MINISTER,  LATER THAT EVENING, ONE OF THE PSYCHOLOGISTS ASKED

ME, WITH SOMETHING LIKE COMPASSIONATE UNDERSTANDING, "YOU ARE
A REDUCTIONIST, AREN'T YOU?" IN THE TONE AN ENLIGHTENED
LIBERAL MIGHT USE TO ASK, "ARE YOU A COMMUNIST?" OR "ARE YOU

A HOMOSEXUAL?H

UPON REFLECTION/IT SEEMS TO ME THAT ANTIREDUCTIONISM IS
AN UNDERSTANDABLE AND PROPER ATTITUDE IN THE SOCIAL SCIENCES,

AFTER ALL, BETWEEN BIOLOGY (INCLUDING PHYSIOLOGICAL PSYCHOLOGY)
AND THE SOCIAL SCIENCES (STARTING WITH SOCIAL PSYCHOLOGY)

THERE EXISTS A TRUE GAP OF SUBJECT MATTER,  THE GAP REFLECTS '

OUR CURRENT IGNORANCE OF THE PHYSICAL AND BIOLOGICAL BASIS

                            .PS
OF HUMAN COGNITION, PHILIP MORRISON, WHO w ONE OF-*Z~+.#
   SPEAKERS, ONCE DEFINED CHEMISTRY AS ,zi
WHILE YOU WAIT FOR THE SCHROEDINGER EQUATION,"

BETWEEN PHYSICS AND CHEMISTRY IS ONLY A TECHNICAL GAP, sFRBd4~-
GAP BETWEEN NATURAL AND SOCIAL SCIENCE IS WIDER, BECAUSE AN

ENTIRE LEVEL OF COMPLEXITY, THAT OF THE HUMAN MIND, REMAINS

TO BE EXPLORED,  SOCIAL SCIENCES DEAL WITH THE STRUCTURE OF

HUMAN SOCIETY, THAT IS, WITH MEN AND WOMEN AS SOCIAL ANIMALS,


5

HUMAN BEHAVIOR IS CONDITIONED BY SOCIETY AS WELL AS BY THE

HUMAN BRAIN,  BUT HOW THE HUMAN BRAIN WORKS STILL ESCAPES

us,  PHYSIOLOGICAL PSYCHOLOGISTS, WHO ARE REALLY BIOLOGISTS,
ARE HARD AT WORK ON THIS, BUT PROGRESS IS SLOW. As A RESULT,

THE SOCIAL SCIENTISTS HAVE TO OPERATE STRICTLY AT THEIR OWN

LEVEL OF PHENOMENOLOGY,            p=cy
         IFI WORR~Q
THEMSELVES ALL THE TIME ABOUT THE POSSIBLE BIOLOGICAL
SUBSTRATE OF THEIR SUBJECT MATTER/THEIR WORK WOULD BE BADLY

HAMPERED,  IN FACT, I BELIEVE THAT SOCIAL SCIENCE IS ACTUALLY

ENDANGERED BY MISGUIDED EFFORTS TO BIOLOGIZE HUMAN BEHAVIOR,
AS I SHALL MENTION LATER IN THIS LECTURE.

     YITWIN BIOLOGY THE ANTI-REDUCTIONIST ATTITUDE HAS NO

     VALID JUSTIFICATION,  IN THIS LECTURE 1 INTEND TO SET FORTH #f
fL##E 5s REDUCTIONIST CREED: NOT A NEGATIVE CREED, THAT DENIES

    THE VALUE OF DEALING WITH PHENOMENA AT THE LEVEL OF

    OBSERVABLE PATTERNS, BUT A POSITIVE REDUCTIONIST CREED,

A POSITIVE REDUCTIONISM IS FOUNDED ON THREE PRINCIPLES,

FIRST, THAT ANY INTERPRETATION OF PHENOMENA AT ANY LEVEL MUST
BE CONGRUENT WITH THE LAWS OF PHYSICS AS GENERAL LAWS OF ' \

NATURE; SECONR, THAT THE INTERPRETATION MUST POTENTIALLY BE

REDUCIBLE TO THE PROPERTIES OF STRUCTURES FULLY INTERPRETABLE


6

IN TERMS OF 38#5 PHYSICAL LAWS, AND JHIRR, THAT IT IS THE

PROPER TASK OF THE SCIENTIST TO FOSTER THE ACHIEVEMENT

OF SUCH REDUCTION,

REDUCTIONISM SHOULD OF COURSE BE HISTORICAL RATHER THAN

MECHANICAL,  To SAY THAT CHEMISTRY OR GEOLOGY OR BIOLOGY MUST

BE INTERPRETABLE IN TERMS OF PHYSICAL LAWS DOES NOT MEAN

THAT THE STARS, THE PLANETS, THE SPECIES THAT EXIST ARE
                c:o vr_p    j3f5 7-I&P
THE ONLY ONES THAT m HAVE &j-33?; AND THAT IF WE KNEW THE

ENTIRE HIS$?RY OF THE UNIVERSE WE COULD CALCULATE THE

ABUNDANCE OF CHEMICAL ELEMENTS ON JUPITER OR THE GENE

FREQUENCIES AMONG PYGMIES IN CENTRAL AFRICA,  WHAT REDUCTIONISM

MEANS IS THE CONFIDENCE THAT THE DECISIVE ELEMENTS IN BIOLOGICAL

EVOLUTION, FROM THE EARLIEST TEMPLATE MOLECULES TO THE MOST

COMPLEX INTERACTIONS BETWEEN SPECIES AND POPULATIONS / HAVE
                                  i

INVOLVED PHYSICAL PROCESSES ONLY; THAT THESE PROCESSES HAVE

NOT BEEN DIFFERENT IN ANY RESPECT FROM THOSE OBSERVED IN

PHYSICAL PHENOMENA; AND THAT ALL BIOLOGICAL PHENOMENA CAN       .

ULTIMATELY BE INTERPRETED IN TERMS OF THE BEHAVIOR OF ATOMIC

AND MOLECULAR STRUCTURES,

THE MOLECULAR BIOLOGY OF THE GENE, TO USE THE FELICITOUS

TITLE OF WATSON'S TEXTBOOK, HAS BROUGHT TO BIOLOGY A UNIFYING

CENTER, COMPARABLE TO THAT PROVIDED TO PHYSICS BY -Q+
THEORY, JUST AS THE ACHIEVEME~~S~A;HYSICS INTERPRET THE

BROAD LINES OF CHEMISTRY WITHOUTfAKING THE EXPLANATION
FULLY EXPLICIT, THE MODERN THEORY OF THE GENE EXPLAINS BIOLOGY
As `6'
WITHOU Y MAKING ALL OF IT EXPLICIT,
    A           WHERE DO WE GO FROM $HERE?


AN ORGANISM OPERATES, NOT WITH GENES BUT WITH GENE

PRODUCTS, THAT IS, WITH PROTEINS,  PROTEINS ARE THE LOVE

OF PROTEIN CHEMISTS, BUT TO THE MOLECULAR BIOLOGIST THEY

ARE A NIGHTMARE,  WHEREAS GENES ARE ALL (OR ALMOST ALL) DNA,

WITH A UNIFORM TAPE-LIKE STRUCTURE AND A CODED SET OF

SPECIFICATIONS AND SIGNALS, PROTEINS START WITH SPAGHETTI-

LIKE FILAMENTS AND FUNCTION ONLY WHEN THE FILAMENTS HAVE

BALLED UP IN THEIR OWN SPECIFIC SHAPES, THOUSANDS OF DIFFERENT

SHAPES,  DESPITE SOME HELPFUL PRINCIPLES, IT STILL TAKES YEARS

OF WORK TO UNRAVEL THE SHAPE OF3 PROTEIN AND THE RELATION
TO ITS FUNCTION,  AT THE MOMENT WE
         /   CAN NO MORE PREDICT THE

PROPERTIES OF A PROTEIN FROM THE SEQUENCES OF ITS AMINO

ACIDS THAN A CHEMIST CAN WRITE THE WAVE EQUATION FOR A NEW

COMPLEX ORGANIC COMPOUND,  THE FRONTIER OF PROTEIN CHEMISTRY

WILL CONTINUE TO BE EXPLORED FOR DECADES, BUT MEANWHILE THE

MOLECULAR BIOLOGIST MUST SEEK OTHER AND GREENER PASTURES,

THE FIRST FIELD I WISH TO TAKE UP IS THAT OF ONTOGENY,

THAT IS, EMBRYOLOGY: THE MAKING OF A COMPLEX ORGANISM OUT

OF CELLS WITH IDENTICAL GENES,  IN A COMPLEX ORGANISM
DIFFERENT GENES'FUNCTION DIFFERENTIALLY IN DIFFERENT CELLS,
     i
IN A UNICELLULAR ORGANISM LIKE A BACTERIUM, DIFFERENTIAL GENE

FUNCTION IS ELICITED DIRECTLY BY THE ENVIRONMENT: SPECIFIC

SUBSTANCES CAUSE THE ACTIVATION OR INHIBITION OF THE FUNCTION

OF SPECIFIC GENES,  WE KNOW HOW THIS IS DONE IN BACTERIA,

BUT WE ALSO KNOW THAT IN THE CELLS OF HIGHER ORGANISMS IT

MUST BE DONE DIFFERENTLY,  \"jE DO NOT YET KNOW HOW, BUT WE

ARE CONFIDENT THAT WE SHALL SOON FIND OUT,


7

BUT WHEN A HUMAN EMBRYO, CONTAINING ONLY A FEW THOUSANDS

CELLS, BEGINS TO TURN SOME OF THESE CELLS INTO PRECURSORS

OF THE BRAIN, OTHERS INTO THE ANCESTORS OF THE GUT, AND

OTHERS STILL INTO THE SOURCES OF MUSCLES AND BONES, THE

SIGNALS CANNOT COME FROM THE OUTSIDE: THEY MUST COME FROM

WITHIN, FROM THE GENES THEMSELVES,  THE SIGNALS MUST BE

PROGRAMMED IN TIME AS WELL AS IN SEQUENCE OF EVENTS,  WHAT
IS THE MOLECULAR BASIS OF THIS PROCESS? SURPRISINGLY, THE

BEST ANALOGY TO DATE COMES FROM CERTAIN VIRUSES,  WHEN

VIRUSES ENTER A SUITABLE CELL THEY UNFOLD A SEQUENTIAL

PATTERN OF EVENTS THAT IS FULLY PROGRAMMED WITHIN THE VIRAL

GENES 1  THIS PROGRAM, WHICH IS REGULATED BY A SERIES OF FEED-

BACK AND FEED-AHEAD COMPONENTS, HAS BEEN ALMOST COMPLETELY

UNRAVELED FOR ONE OR TWO VIRUSES,  IT SUGGESTS AT LEAST

THE KINDS OF MECHANISMS THAT COULD BE INVOLVED IN
  4i/

EMBRYOGENESIS: TURNINGdN MECHANISMS SPECIFIC FOR ACTIVATING
                         7% E:N     OR OFF
A GROUP OF GENES, WHOSE PRODUCTS CAN m
GENE SETS, &u?( ti&k'Lv        TURN ONnOTHER

IN EMBRYOLOGY, HOWEVER, THERE IS THE ADDED PROBLEM OF

DIFFERENTIATION,  THE PROGRAM PRESCRIBES, NOT ONLY WHEN AND

            IN WHICH SEQUENCE THE CHANGES OCCUR, BUT WHERE: THAT IS,
       WHICH CELLS OR GROUPS OF CELLS WILL GO IN WHICH DIRECTION, 4NJ %/g
                                                                           -

                                                  SOMETHING OF A

OF COMPLEXITY FROM WHAT MOLECULAR BIOLOGISTS

IN BACTERIA-,  THE SITUATIONS THAT

ARE RELEVANT TO DIFFERENTIATION ARE NOT LIKE THOSE IN WHICH


8

ONE GENE IS TURNED ON OR OFF ACCORDING TO HOW MUCH OF ITS

PRODUCT IS NEEDED IN A GIVEN ENVIRONMENT,  THE ESSENCE OF

DIFFERENTIATION IS STABILITY AND OFTEN IRREVERSIBILITY,
SUPERFICIALLY AT LEAST, THE BACTERIAL SITUATION DIFFERS FROM

DIFFERENTIATION IN HIGHER ORGANISMS AS A TELEPHONE CALL

DIFFERS FROM A WEDDING,  AT THE MOLECULAR LEVEL, IN OTHER

WORDS, WE KNOW HOW SWITCHES ARE TURNED ON AND OFF'BUT WE DO

NOT YET KNOW HOW CELLS MAKE COMMITMENTS ?!J LAST &ILL DEATH
m THEM PART,  FOR THAT REASON, EMBRYOLOGY HAS REMAINED

PHENOMENOLOGICAL, NONREDUCTIONIST FOR A VERY LONG TIME,
NOW, HOWEVER, THIS CITADEL BEGINS TO YIELD TO THE STRATEGIES

OF MOLECULAR BIOLOGY, THAT IS, TO THE CONCERTED APPLICATION

OF GENETIC AND BIOCHEMICAL ANALYSES,

ESSENTIALLY, WHAT IS BEING DONE IS TO BREAK DOWN THE

COMPLEX SITUATION INTO MANY, POTENTIALLY LESS COMPLEX

ELEMENTS,  iF THE PROBLEM OF HOW GENES ARE REGULATED IN THE

CELLS OF HIGHER ORGANISMS STILL BAFFLES US, WE TURN FIRST

TO THE MOLECULAR ORGANIZATION OF CHROMOSOMES, WHERE THE

GENES ARE LOCATED,  ONE BEGINS BY HOMOLOGIZING SPECIFIC

STRUCTURES WITHIN CHROMOSOMES WITH THE LOCATION AND SIZE

OF THE GENES,  ONE IDENTIFIES THE PROTEINS OF THE CHROMOSOMES,

HOPING TO UNDERSTAND WHICH OF THEM ARE INVOLVED IN REGULATION

OF GENE ACTIVITY,  ONE CAN ISOLATE THE PRIMARY MESSAGES THAT

CODE FOR PROTEINS MADE BY SPECIFIC DIFFERENTIATED CELLS,

THIS TELLS us THAT THE MESSAGES ARE IN FACT SPECIFICALLY


MADEiN THOSE CELLS, RATHER THAN MADE IN ALL CELLS AND
SPECIFICALLY USED ONLY IN SOME CELLS,

THE METHODS OF GENETIC ENGINEERING CURRENTLY UNDER

DEVELOPMENT, ATTACHING PIECES OF n!`i4 FROM CELLULAR CHROMO-
                     Mfl-7

SOMES TO INA DERIVED FROM BACTERIA,- LEAD&&

FURTHER TOWARD THE ISOLATION OF THE PIECES OF CHROMOSOME

THAT CONTAIN SPECIFIC GENES,

BESIDES PURSUING THE GENES IN ACTION BY WAY OF CHROMO-

SOME STRUCTURE, THE MOLECULAR BIOLOGIST IS AFTER THE SECRETS

OF DIFFERENTIATION BY STUDYING THE SIGNALS THAT CAUSE

DIFFERENT CELLS TO ACT IN SPECIFIC WAYS AND TO BECOME

COMMITTED TO DIFFERENT DESTINIES,  THE PROBLEM IS STILL

BEWILDERING, NOT FOR LACK OF CLUES, BUT BECAUSE OF THEIR

ABUNDANCE AND VARIETY,  PROTEIN FACTORS, PEPTIDES, AND

STEROID HORMONES ELICIT IN DIFFERENT CELLS OF THE ADULT

ORGANISM OR OF THE EMBRYO SUCH A VARIETY OF SPECIFIC

RESPONSES THAT MAY AT FIR T SEE TO PROMISE NOTHING BUT
      I%43 j&@Jfll
CHAOS,  BUT THE CHAOS     6 YIELD TO BIOCHEMICAL

DISSECTION,     E OF THE MYSTERY DISAPPEARS AS THE PROCESS

                        ER OF A CELL WITH AN EXTERNAL

                      OKEN DOWN INTO A SERIES OF

STEPS,  FOR EXAMPLE, A STEROID HORMONE MUST ENTER A CELL

AND COMPLE/X WITH A CYTOPLASMIC PROTEIN,  THE COMPLEX --

NOT EITHER OF THE TWO COMPONENTS SEPARATELY -- THEN MOVES

TO THE CELL NUCLEUS AND ACTIVATES SPECIFIC GENES,  THE


10

DIFFERENT RESPONSES OF DIFFERENT CELLS MAY REFLECT DIFFERENCES

IN ENTRY OF THE HORMONE, OR IN ITS COMBINATION WITH CARRIER

PROTEIN, OR IN THE AFFINITY FOR VARIOUS CHROMOSOMAL SITES,

OR IN THE RESPONSE OF INDIVIDUAL GENES,  THE LAST POSSIBILITY

SEEMS TO BE THE IMPORTANT ONE: IN THOSE CELLS THAT RESPOND

TO THE HORMONE, THE HORMONE-CARRIER C MPLEX BINDS TO
               6

HUNDREDS OF CHROMOSOMAL SITES, BUT ONLY ONE OR A FEW GENES

RESPOND,  EVIDENTLY, THE GENE SET IS PROGRAMMED TO RESPOND

SPECIFICALLY TO A RELATIVELY UNSPECIFIC STIMULUS,  How? WE

HOPE THE ANSWER WILL COME SOON,

THE THIRD AND MOST POWERFUL REDUCTIONIST APPROACH TO

EMBRYOLOGY IS BY GOING FROM ORGANISMS OR ORGANS TO CULTURES

OF CELLS,  APART FROM THE RANGE OF EXPERIMENTATION THAT

CELL CULTURES MAKE POSSIBLE ON THE PROBLEMS 1 HAVE ALREADY

MENTIONED --  CHROMOSOME-GENE RELATION AND GENE-SIGNAL

INTERACTION --  CELL CULTURES MAKE IT POSSIBLE TO ANALYZE A
KEY ASPECT OF DEVELOPMENT, THE CONTROL OF CELL PROLIFERATION, f
FOR IN THE COURSE OF DEVELOPMENT, DIFFERENTIATION IS

INTIMATELY TIED UP WITH CONTROLLED PROLIFERATION,  AT ONE

EXTREME, CELLS LIKE NEURONS OR MUSCLE FIBERS DO NOT DIVIDE
ANY MORE IN THE ADULT BODY, EVEN WHEN THEY STILL PROLIFERATE,

DURING EMBRYOGENESIS, THEY PROLIFERATE IN A CONTROLLED WAY,

WHICH GENERATES THE SPECIFIC SIZES AND SHAPES OF THE ORGANS,
AT THE OTHER EXTREME ARE STEM CELLS, WHICH CONTINUE TO PROLI-

FERATE THROUGHOUT LIFE, BUT ONLY IN A LINEAR FASHION:


11

FOR EXAMPLE, WHEN A STEM CELL OF THE SKIN DIVIDES, IT

GENERATES ONE STEM CELL AND ONE CELL COMMITTED TO DIFFEREN-

TIATION,  THIS COMMITTED CELL WILL NO MORE DIVIDE, BUT

WILL CHANGE INTO A HORNY SKIN CELL AND THEN DIE,

DIFFERENTIATION, THEREFORE, IS CLOSELY TIED TO CONTROL OF

CELL PROLIFERATION,  THE CANCER PROBLEM, INCIDENTALLY, IS

A VARIATION ON THIS THEME,

  CULTURED CELLS ARE AN INEXHAUSTIBLE SOURCE OF INFORMATION

IN THIS RESPECT, THEY MAKE ITPOSSIBLE TO CLARIFY THE CONNECTION

BETWEEN THE CELL CYCLE FROM ONE DIVISION TO THE NEXT AND THE

PROCESS OF GENE DUPLICATION,  THEY HAVE REVEALED THE ROLE

OF HORMONES AND OTHER SUBSTANCES ON THE TRIGGERING AND

INHIBITING OF THE CYCLE,  THEY HAVE REVEALED THE UNSUSPECTEDLY

CENTRAL ROLE THAT THE OUTER MEMBRANE OF THE CELL PLAYSAN

ACTIVATING VARIOUS PHASES OF CELL PROLIFERATION,  THE

MOLECULAR BIOLOGY OF THE CELL MEMBRANE HAS BECOME A CENTRAL

ASPECT OF THE STUDY OF DIFFERENTIATION,  FOR EXAMPLE, THE

SPECIFIC DIFFERENTIATION OF BONE MARROW STEM CELLS INTO RED-

BLOODICELLwPRECURSORS: IS /   TRIGGERED, IN CELL CULTURE AS WELL

AS IN THE INTACT ORGANISM, BY A PROTEIN CALLED Em,

-WHICH NEVER ENTERS THE CELL BUT COMBINES WITH A SPECIFIC

MEMBRANE SITE,  THE SAME CELL, IN RESPONSE TO A DIFFERENT

STIMULUS, WOULD HAVE GENERATED WHITE BLOOD CELLS,  EVIDENTLY,

THE MEMBRANE OF THE UNDIFFERENTIATED BONE MARROW CELL HAS A

MULTIPLICITY OF RECOGNITION SITES, WITH SPECIFIC AFFINITIES


12

FOR DIFFERENT SIGNAL MOLECULES, EACH OF WHICH TRIGGERS A

DIFFERENT RESPONSE -- THAT IS, ACTIVATES A DIFFERENT SET

OF GENES,

  4T THIS POINT THE MOLECULAR BIOLOGIST FEELS EXCITED,
HE HAS NOT YET BROKEN THE CODE OF DIFFERENTIATION, AS HE

HAD SUCCESSFULLY BROKEN THE GENETIC CODE AND THE SIGNAL

CODE OF BACTERIAL GENE FUNCTION,  BUT THE FORTRESS IS

BEGINNING TO CRUMBLE,
            idG WHAT IS NEEDED NEXT, AND IS &I L (E&J~

e BECOME AVAILABLE, IS A SET OF SYSTEMS SIMPLI-
FIED ONE STEP FURTHER: SYSTEMS IN WHICH A PIECE OF CHROMOSOME,

PLACED IN A TEST TUBE WITH THE APPROPRIATE ENZYMES AND

FACTORS, WILL GENERATE ITSAMESSAGE AND ITS PROTEIN PRODUCT,
THEN THE ROLE OF THE STIMULANTS OR INHIBITORS THAT ACT DURING

DEVELOPMENT AND IN VARIOUS ADULT ORGANS WILL BECOME TESTABLE,
1 PREDICT THE FIRST OUTPUTS OF THIS PROGRAM ARE LESS THAN

FIVE YEARS AWAY AND THE MOLECULAR UNDERSTANDING OF THE

CONTROLS OF CELL PROLIFERATION LESS THAN TEN,

  IF UNDERSTANDING EMBRYOLOGY, THAT IS, UNRAVELING THE

PROGRAM THAT MAKES ALL OF US WHAT WE ARE IN OUR GROWTH,

HEALTH, ILLNESSES, AND DEATH SEEMS A STAGGERING TASK, THE

OTHER TASK THAT   PROPOSE FOR MOLECULAR BIOLOGISTS IS

POSSIBLY MORE DIFFICULT,  1 REFER TO THE MOLECULAR

INTERPRETATION OF EVOLUTION,


13

EVOLUTION, OF COURSE, TAKES TIME, IT TOOK FOUR

BILLION YEARS OF EARTH HISTORY TO PRODUCE ANIMALS; IT
TOOK 200 MILLION YEARS TO GENERATE MAMMALS FROM THEIR

REPTILE ANCESTORS; IT MAY HAVE TAKEN TWENTY MILLION YEARS
TO GENERATE MAN FROM OUR COMMON ANCESTORS WITH TODAY'S

LIVING APES,

  SUPERFICIALLY, THERE WOULD SEEM TO BE NO GREAT HURRY TO

FIND OUT HOW ALL THIS HAPPENED,  IT IS NOT LIKELY TO START

HAPPENING MUCH FASTER, NOR IS THERE MUCH WE CAN DO ABOUT IT

EXCEPT BEING SENSIBLE ABOUT ATOM BOMBS AND POLLUTION,  BUT

THIS IS NOT THE WHOLE STORY,  WE DO HAVE A STAKE IN

UNDERSTANDING THE MECHANISMS OF EVOLUTION, AND UNDERSTANDING

THEM SOON, BECAUSE THE CONSEQUENCES OF EVOLUTION ARE

PRESSINGLY UPON US, MATERIALLY, MORALLY, AND INTELLECTUALLY,

ALL THE TIME,

SINCE DARWIN'S TIME WE UNDERSTAND THE GRAND LINES OF         I

EVOLUTION: VARIATION PROVIDES THE MATERIAL UPON WHICH NATURAL

SELECTION PLAYS,  BUT THIS AWARENESS OF THE MAIN FORCES IS

ABOUT AS ILLUMINATING TO AN EVOLUTIONIST AS QUANTUM

MECHANICS IS TO A CHEMIST,  WHICH VARIATIONS CONTRIBUTE

TO THE EMERGENCE OF NEW SPECIES? BY WHAT COMBINATION OF

EVENTS DO SOME LINES OF DESCENT PETER OUT, OTHERS BECOME

IMMOBILIZED, OTHERS STILL BLOSSOM INTO THOUSANDS OF
DIRECTIONS? A PRESSING QUESTION IS THAT OF THE TIME SCALE

OF EVOLUTION,  IS THAT SCALE CONGRUENT WITH THE TIME


14

PARAMETERS OF VARIATION AND SELECTION AS WE MEASURE THEM?

AND ARE VARIATION AND SELECTION INDEPENDENT FORCES, THE

LATTER JUST ACTING ON THE OUTPUT OF THE FORMER, OR ARE

THEY TIED TOGETHER INTO AN INTERACTING SYSTEM BY STRUCTURAL

FEEDBACKS?

FOR MANY YEARS BIOCHEMISTS HAVE COMPARED A FEW HOMOLOGOUS

PROTEINS, THAT IS, PROTEINS WITH SIMILAR FUNCTION IN

ORGANISMS RANGING ALL THE WAY FROM YEASTS TO HUMANS,  THIS

IS LIKE STUDYING THE HISTORY OF SPECIFIC GENES,  THROUGH

THIS KIND OF MOLECULAR EVOLUTIONARY HISTORY THE AMOUNT OF

VARIATION PER UNIT OF GEOLOGICAL TIME CAN BE ESTIMATED,

1 WILL NOT GO HERE INTO THE QUESTIONS OF CALCULATING THE RATE

OF EVOLUTION FROM THESE DATA, EXCEPT TO SAY THAT THE RESULTS

NOT ONLY FIT QUITE WELL THE CLASSIFICATION PROPOSED BY

TAXONOMISTS, BUT ALSO THE TIME SCALE OF PALEONTOLOGISTS,

THE HARD PROBLEMS COME UP, HOWEVER, WHEN WE COME TO THE BIG

QUESTIONS: THE ORIGIN OF N W GE  S, THE lo&FOLD DIFFERENCE     I
        jeh-d%

IN AMOUNT OF DNA AND OF GENES <FROM YEAST TO MAMMALS, AND,
                 r\

MORE DRAMATIC, THE RAPID EVOLUTION OF CERTAIN LINES OF

DESCENT AT SPECIFIC TIMES,

  NOT SURPRISINGLY, NAIVE CALCULATIONS BASED ON DATA
AVAILABLE AS RECENTLY AS 10 YEARS AGO LAND US INTO TROUBLE,

THE MUTATIONS THAT THE GENETICIST KNOWS BEST -- CHANGES OF

INDIVIDUAL DIGITS OF THE GENETIC SCRIPT OR REARRANGEMENTS

OF PIECES OF CHROMOSOME --  SEEM TO BE NEITHER FREQUENT

ENOUGH NOR VARIED ENOUGH TO REASSURE THE EVOLUTIONIST THAT


                           15
ddd

THEY- THE WHOLE STORY OF GENETIC VARIATION,  HENCE,

HYPOTHESES OF UNKNOWN FORCES, OR OF LIFE HAVING BEEN

IMPORTED FROM OUTER SPACE TO COLONIZE THE EARTH, HAVE

BEEN SERIOUSLY ENTERTAINED,

FORTUNATELY, THE SITUATION HAS IMPROVED IN TWO IMPORTANT

WAYS, FIRST, M;E;YLAR BIOLOGISTS HAVE UNCOVERED THE
EXISTENCE OF- KINDS OF GENETIC VARIATION THAT MAY

SERVE TO SPEED UP EVOLUTION BY GENERATING A GREATER VARIETY

OF CHANGES,  AMONG THEM ARE, TO NAME A FEW, MUTATOR GENES;

THAT CAUSE THE FREQUENCY OF MUTATION TO INCREASE BY A

FACTOR OF 10 OR 100; GENETIC CONTROL OF CROSSING OVER,

WHICH MAY ALTER THE FREQUENCY OF RECOMBINATION; INSERTION

SEQUENCES, WHICH PERMIT THE INSERTION OF FRAGMENTS OF

GENETIC MATERIAL INTO CHROMOSOMES AND BRING ABOUT NEW

GENE COMBINATIONS; AND CONTROLLING ELEMENTS, WHICH CAN
                  QORE~:P,LESS ~E~ZPIAP~/VTL~ J
        UPS- iN                    _ .-_---w-'
            /c  DIFF-ERENT LINES OF
    THESE/AND OTHER PROCESSES THAT MAY STILL AWAIT         '

DESCENT,

DISCOVERY&kkkpROVIDE A GREATER RANGE OF GENOTYPES FOR
  /
NATURAL SELECTION TO ACT UPON,

BUT THE PROBLEM OF THE SPURTS OF FAST EVOLUTION STILL

REMAINS,  THESE ARE INSTANCES IN WHICH EVOLUTION SEEMS TO

HAVE PERSISTENTLY CONCENTRATED ON IMPROVING SOME SPECIFIC

DEVICE, IGNORING EVERYTHING ELSE, LIKE A GAMBLER WHO BETS

ALL ON ONE HORSE OVER AND OVER AGAIN,  IN THIS WAY

EVOLUTION BRINGS ABOUT ASTONISHING CHANGES,  AN ELECTRIC


16

FISH, WHICH GENERATES AND MONITORS AN ELECTRIC FIELD FOR

ITS OWN NOURISHMENT AND PROTECTION, HAS IN ITS BRAIN AN

                 IS ENTIRELY DEVOTED TO DECODING AND
                                   *r" -------__/-------
EMITTING ELECTRIC SIGNALS,
__,^. /- -..-. ..-- -
>/ELECTRIC    -.. _
   RELATIVES, &RE.  $~HICH Is MISSING IN ITS~
                                    THE HUMAN BRAIN

IN LESS THAN ONE MILLION YEARS TO

ALMOST DOUBLE ITS SIZE, CONCOMITANT WITH THE DEVELOPMENT

OF HUMAN MENTAL FACULTIES, ESPECIALLY LANGUAGE,

THE PROBLEM OF SUCH EVOLUTIONARY SPURTS IS UNRESOLVED~'

BECAUSE THE MECHANISMS ARE NOT YET KNOWN, BUT IT IS NOTI

INSOLUBLE, WE REALIZE NOW/THAT WHAT IS NEEDED IS SOME
ADDITIONAL FEEDBACK, SUCH hS COULD BE PROVIDED BY A TIE-UP

BETWEEN RATES OF VARIATION AND OF SELECTION,  IF, AT

SPECIFIC TIMES AND IN SPECIFIC ENVIRONMENTS, SELECTION
WERE FAVORING A CERTAIN CLASS OF GENOTYPES (FOR EXAMPLE, MORE
COMPLEX CEREBRAL FUNCTIONS) AND IF THE SELECTIVE VALUE OF

THOSE GENOTYPES WERE ENHANCED BY INCREASED RATES OF GENETIC

VARIATION OR RECOMBINATION, THEN SELECTION WOULD FAVOR

ENHANCED VARIABILITY AND ACCELERATE THE RATE OF EVOLUTION

IN A NON-LINEAR WAY,  SUCH A COUPLED SELECTIVE PRESSURE, ON

GENETIC VARIABILITY AND ON A SPECIFI  CLASS
     i     OF GENOTYPES,

MAY HAVE CONTRIBUTED TO THE RAPID EV  LUTION  OF HOMINIDS,

AND MAY ALSO EXPLAIN THE HIGH DEGREE OF POLYMORPHISM OF THE

HUMAN SPECIES COMPARED TO OTHER PRIMATES,  (A CONVINCING

ANALYSIS OF THE CONCEPT OF SELECTION FOR VARIABILITY HAS
RECENTLY BEEN PRESENTED BY PROFESSOR LAYZER),


17

AN UNDERSTANDING OF THESE PHENOMENA, MORE PARTICULARLY

A CLARIFICATION OF FEEDBACKS BETWEEN VARIATION AND SELECTION,

IS IMPORTANT FOR SEVERAL REASONS,  ONE OF THEM IS THE NEED
TO DISPEL CONFUSIONS THAT ARISE WHEN PEOPLE DEAL WITH HUMAN

FACULTIES IN A BIOLOGICAL WAY,  IF ONE IGNORES THE HIGH

RATES OF EVOLUTION THAT BRING ABOUT A DOMINANT SPECIES LIKE
MAN, THERE CREEPS INTO BIOLOGY A TENDENCY TO HOMOLOGIZE

TRAITS AND BEHAVIORS BETWEEEN DIFFERENT SPECIES, ORDERS,

OR PHYLA, AS THOUGH EVOLUTION HAD STAYED PUT IN SOME WAYS

WHILE MOVING RAPIDLY IN OTHER WAYS,  THUS SOME ETHOLOGISTS h/n/&

P

FROM OBSERVATIONS OF INSTINCTUAL AGGRESSIVITY IN

INSECTS OR FISHES, TO INTERPRETING VIOLENCE AMONG HUMANS AS

RESULTING FROM COMPARABLE MECHANISMS,  SOCIOBIOLOGISTS MAY

JUMP FROM DESCRIPTIONS OF RELATIONS BETWEEN MEMBERS OF ONE

SPECIES TO SIMPLISTIC INTERPRETATIONS OF THE BEHAVIOR OF

OTHER SPECIES,  THIS IS UNJUSTIFIED AND, AT TIMES,

  I                    5 ErLIJ+ti -l- 1 e
IRRESPONSIBLE, THE M IMPLICATIONS OF M~ONFUSIONJ

BETWEEN BIOLOGY AND HUMAN AFFAIRS CAN BE OMINOUS,  LOOSE

TALK OF GENES FOR AGGRESSION IN A STICKLEBACK FISH `MAY BE
                                /

RIGHT OR WRONG, BUT IS CERTAINLY INNOCUOUS,  To SUGGEST,

HOWEVER, THAT THERE ARE GENES OR CHROMOSOME FOR VIOLENT

BEHAVIOR IN HUMANS IS NOT A BIOLOGICAL STATEMENT: IT IS A

SOCIOPOLITICAL&TIQN_I  IT IS AN INCURSION INTO THE FIELD

OF VALUES, AN INCURSION THAT MAY INFLUENCE THE TREATMENT

OF INDIVIDUALS AND THE PASSAGE OF LEGISLATION ON SOCIAL

PROBLEMS,  SUFFICE IT TO RECALL HOW FIFTY YEARS AGO THE

INSISTENCE OF SOME BIOLOGISTS TO IDENTIFY PELLAGRA AS A


18

GENETIC DISEASE OF THE
     .__.   --------

EVIDENCE THAT PELLAGRA WAS A VITAMI

FOR DECADES THE PROPER SOCIAL INTERVENTION AT THE

NUTRITIONAL LEVEL,

  As WE BIOLOGISTS APPROACH THE STUDY OF EVOLUTION OF OUR

OWN SPECIES WE OUGHT TO BE MINDFUL OF WHA
CALLED "THE HUMAN NATURE OF HUMAN NATURE" -- OF THE FACT THAT,

IN BRINGING ABOUT LANGUAGE AND MIND, EVOLUTION HAS CREATED A

COMPLETELY NOVEL AND UNIQUE SET OF FORCES -- CULTURY AND
TRADITION, AND VERBALIZABLE IMAGINATION,

      $1~0        THESE FO#RCES HAVE
NOT ISOLATED MAN~ROM ITS BIOLOGICAL NATURE, BUT HAVE
SUPERIMPOSED UPON IT A NEW LEVEL, THAT OF COGNITION, 32&47Inj~,cti

CONDITIONS AND FILTERS ALL HUMAN ACTIVITIES,  ANY ATTEMPT

TO SINGLE OUT BEHAVIORS FOR BIOLOGICAL INTERPRETATIONS MUST,
     Et/3 LJ4 I--

NOT ONLY -SOCIAL AND CULTURAL INFLUENCES, BUT TAKE

ACTIVELY INTO ACCOUNT THE INTERPLAY BETWEEN BIOLOGICAL AND

CULTURfAL FACTORS,  JUST AS IN THE BIOLOGY OF DOMESTIC ANIMALS

OR PLANTS WE CANNOT IGNORE THE ROLE THAT MAN f(`dJJ
           d
                                     S PLAYED, SO

IN ATTEMPTING TO BIOLOGIZE HUMAN BEHAVIOR WE MUST BE AWARE
THAT IN MAN EVEN BIOLOGY IS SUBJECT TO CULTURE AND
   I

UNDERSTANDING,

  IN CLOSING, LET ME SINGLE OUT ONE FRONTIER THAT TODAY
MAY SEEM AS UNREACHABLE AS MOUNT EVEREST SEEMED TO BE 50

YEARS AGO,  AND YET, IT IS EXCITING ENOUGH TO WARRANT

SERIOUS ATTENTION,  1 REFER TO WHAT 1 MAY CALL BIOLINGUISTICS,


19

OR THE BIOLOGY OF HUMAN LANGUAGE,  THE REASON FOR SINGLING

OUT THIS FIELD IS TWO-FOLD,  FIRST, HUMAN LANGUAGE 1s THE

SPECIAL FACULTY THROUGH WHICH ALL CONSCIOUS HUMAN ACTIVITY

IS FILTERED; A FACULTY WHOSE DEVELOPMENT MAY WELL HAVE

PLAYED THE DRIVING ROLE IN THE ALMOST CATASTROPHIC EVOLUTION

FROM APE-KIND TO HUMANKIND,  AND SECOND,  LANGUAGE ALONE,

AMONG THE UNIQUELY HUMAN

3 pfe  SCIENTIST A SYSTEMATIC THEORY, THE STRUCTURAL LINGUISTICS
             cs/L/U/L~J 4 y &v/I &IS

/, DEVELOPED BY4

  CONFRONTATION WITH BIOLOGICAL      HAT 1 MEAN IS THAT

FORMAL LANGUAGE STRUCTURE, PLUS SOME FACTS ALREADY KNOWN

ABOUT LANGUAGE AND BRAIN STRUCTURE, PLUS THE ADVANCING

  -\ KNOWLEDGE OF BRAIN ORGANIZATION PROVIDED BY PHYSIOLOGISTS, :e
`TR47 my :i  HOLD SOME PROMISE THAT BETWEEN LINGUISTICS AND NEUROBIOLOGY

if% 6 b'?D&              ERGENCE MAY SOON BE POSSIBLE,-t+KE T%

P l&D@                                        MAL GtNl7333-

                                                                           In.
/m=-0 nfE                        K B1oL-
                                                                           I

TOO FAR INTO THE FUTURE,  BUT, AS I MENTIONED AT THE START,

1 AM TOO OLD TO LOOK ANYWHERE BUT AHEAD,


19

OR THE BIOLOGY OF HUMAN LANGUAGE,  THE REASON FOR SINGLING

OUT THIS FIELD IS TWO-FOLD, FIRST, HUMAN LANGUAGE IS THE

SPECIAL FACULTY THROUGH WHICH ALL CONSCIOUS HUMAN ACTIVITY

IS FILTERED; A FACULTY WHOSE DEVELOPMENT MAY WELL HAVE

PLAYED THE DRIVING ROLE IN THE ALMOST CATASTROPHIC EVOLUTION

FROM APE-KIND TO HUMANKIND,  AND SECOND, LANGUAGE ALONE,

AMONG THE UNIQUELY HUMAN FACULTIES OF THE HUMAN BRAIN, OFFERS

TO THE SCIENTIST A SYSTEMATIC THEORY, THE STRUCTURAL
LINGUISTICS DEVELOPED BY CHOMSKY AND HIS COLLEAGUES, WHICH

MAY BE AMENABLE TO CONFRONTATION WITH BIOLOGICAL DATA,  WHAT

1 MEAN IS THAT FORMAL LANGUAGE STRUCTURE, PLUS SOME FACTS

ALREADY KNOWN ABOUT LANGUAGE AND BRAIN STRUCTURE, PLUS THE

ADVANCING KNOWLEDGE OF BRAIN ORGANIZATION PROVIDED'BY

PHYSIOLOGISTS, HOLD SOME PROMISE THAT BETWEEN LINGUISTICS

AND NEUROBIOLOGY A KIND OF CONVERGENCE MAY SOON BE POSSIBLE,

LIKE THE CONVERGENCE WHICH FORTY YEARS AGO BROUGHT FORMAL

GENETICS TOGETHER WITH BIOCHEMISTRY TO CREATE MOLECULAR

BIOLOGY,

  1 FEEL IN THE AUDIENCE A MOVEMENT OF IMPATIENCE, AS IF

1 HAD PUSHED SPECULATION TOO FAR, PROJECTING BIOLOGY INTO

A TOO DISTANT FUTURE,  As 1 MENTIONED AT THE START, I AM

TOO OLD TO LOOK ANYWHERE BUT AHEAD,